Originally published as Genetics Published Articles Ahead of Print on February 2, 2009.

Genetics, Vol. 181, 1415-1425, April 2009, Copyright © 2009
doi:10.1534/genetics.108.095240

A Domestic cat X Chromosome Linkage Map and the Sex-Linked orange Locus: Mapping of orange, Multiple Origins and Epistasis Over nonagouti

Anne Schmidt-Küntzel^*,,1, George Nelson^*, Victor A. David, Alejandro A. Schäffer, Eduardo Eizirik^,**,, Melody E. Roelke^*, James S. Kehler, Steven S. Hannah, Stephen J. O'Brien and Marilyn Menotti-Raymond

^* Laboratory of Genomic Diversity, Science Applications International Corporation and Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702, Genetics Department, George Washington University, Washington, DC 20037, National Center for Biotechnology Information, National Library of Medicine and Department of Health and Human Services, National Institutes of Health, Bethesda, Maryland 20894, ^** Faculdade de Biociências, Pontifica Universidade Católica do Rio Grande do Sul, Porto Alegre, RS-900, Brazil, Instituto Pró-Carnivoros, Atibaia, 12945-010, Brazil, and Nestlé Purina PetCare, Saint Louis, Missouri 63102

¹ Corresponding author: Bldg. 560, Room 11-38, National Cancer Institute, Frederick, MD 21702.
E-mail: anne.c.sk{at}gmail.com

A comprehensive genetic linkage map of the domestic cat X chromosome was generated with the goal of localizing the genomic position of the classic X-linked orange (O) locus. Microsatellite markers with an average spacing of 3 Mb were selected from sequence traces of the cat 1.9x whole genome sequence (WGS), including the pseudoautosomal region 1 (PAR1). Extreme variation in recombination rates (centimorgans per megabase) was observed along the X chromosome, ranging from a virtual absence of recombination events in a region estimated to be >30 Mb to recombination frequencies of 15.7 cM/Mb in a segment estimated to be <0.3 Mb. This detailed linkage map was applied to position the X-linked orange gene, placing this locus on the q arm of the X chromosome, as opposed to a previously reported location on the p arm. Fine mapping placed the locus between markers at positions 106 and 116.8 Mb in the current 1.9x-coverage sequence assembly of the cat genome. Haplotype analysis revealed potential recombination events that could reduce the size of the candidate region to 3.5 Mb and suggested multiple origins for the orange phenotype in the domestic cat. Furthermore, epistasis of orange over nonagouti was demonstrated at the genetic level.

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